{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:54:39Z","timestamp":1791888879934,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The association between relapse and remodeling of the bone marrow immune microenvironment in pediatric B\u2010cell acute lymphoblastic leukemia (B\u2010ALL) remains incompletely understood. This study aims to characterize the transcriptional and cellular alterations associated with B\u2010ALL relapse and identify immune\u2010related genes (IRGs) associated with disease recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bulk (GSE3910 and GSE28460) and single\u2010cell RNA sequencing (scRNA\u2010seq) (GSE130116) data were obtained from the GEO database, whereas IRGs were retrieved from ImmPort database. GSE3910 dataset was analyzed to identify differentially expressed genes (DEGs), followed by functional enrichment and immune infiltration analysis. scRNA\u2010seq data were used for cell annotation and cell\u2013cell communication analysis to identify key immune shifts. Candidate genes were identified through the intersection of scRNA\u2010seq DEGs, bulk RNA sequencing (bulk RNA\u2010seq) DEGs, and IRGs. Gene\u2013gene interaction (GGI) and transcription factor analyses, and external validation using GSE28460 were subsequently performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 544 DEGs were identified from DEG3910. Functional enrichment analysis indicated that relapse was associated with enhanced cell proliferation, immune stress, and inflammatory responses. scRNA\u2010seq analysis revealed substantial microenvironmental heterogeneity. Cell\u2013cell communication analysis identified alternations in signaling networks during relapse, particularly toward T and natural killer cells. Pathways related to prostaglandin and NEGR signaling were notably enriched in relapse samples. Integrative analysis identified seven IRGs (\n                      <jats:italic>ELANE<\/jats:italic>\n                      ,\n                      <jats:italic>S100A8<\/jats:italic>\n                      ,\n                      <jats:italic>MNDA<\/jats:italic>\n                      ,\n                      <jats:italic>S100A9<\/jats:italic>\n                      ,\n                      <jats:italic>S100A12<\/jats:italic>\n                      ,\n                      <jats:italic>PSAP<\/jats:italic>\n                      , and\n                      <jats:italic>FCN1<\/jats:italic>\n                      ) associated with relapse and were predominantly associated with myeloid cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Relapsed pediatric B\u2010ALL may be associated with heterogeneous alterations in immune microenvironment and intercellular communication. The identified genes may represent relapse\u2010associated molecular features and warrant further functional investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70741","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:41:32Z","timestamp":1791888092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Bulk and Single\u2010Cell RNA Sequencing Reveals Alterations in the Immune Microenvironment and Candidate Immune\u2010Related Genes Associated With Diagnosis and Relapse in Childhood B\u2010Cell Acute Lymphoblastic Leukemia"],"prefix":"10.1002","author":[{"given":"Lin","family":"Han","sequence":"first","affiliation":[{"name":"Department of Emergency Jinan Children's Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Hematology Binzhou People's Hospital  Binzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Jinan Children's Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongling","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Emergency Jinan Children's Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8987-0226","authenticated-orcid":false,"given":"Qingwei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology and Department of Child Health Jinan Children's Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.12703\/p6\u201059"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(19)30031\u20102"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.12659\/msm.923271"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9548.1"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2025.0006"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13071536"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.04.015"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15186"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010023\u201001428\u20102"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102020\u2010139028"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00147"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.188891"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1187741"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102006\u201002\u2010002824"},{"issue":"7","key":"e_1_2_14_16_1","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkv007","article-title":"Limma Powers Differential Expression Analyses for RNA\u2010Sequencing and Microarray Studies","volume":"43","author":"Ritchie M. E.","year":"2015","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr260"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac947"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.04.015"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201021246\u20109"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010017\u20101349\u20101"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq537"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz240"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010022\u201003858\u2010x"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010022\u201001561\u20105"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576\u2010020\u201000292\u2010x"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010025\u201003133\u2010y"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1743920"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16657"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22136665"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.8052"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15123090"},{"issue":"7","key":"e_1_2_14_35_1","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1158\/1538-7445.AM2026-2088","article-title":"Prostaglandin E2 Signaling Promotes Adverse Survival Outcome in B\u2010Cell Acute Lymphoblastic Leukemia","volume":"86","author":"Cohen M.","year":"2026","journal-title":"Cancer Research"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci129204"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13777"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1395035"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010021\u201000766\u20102"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13722"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26051323"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2023.2193855"},{"key":"e_1_2_14_43_1","first-page":"3153","article-title":"ELANE Is Highly Expressed in Leukemia Patients and Predicts Poor Survival","volume":"12","author":"Zaho Y.","year":"2019","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1395035"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.70085"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1425075"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1545-5017.70741","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/1545-5017.70741","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1545-5017.70741","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:41:34Z","timestamp":1791888094000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/1545-5017.70741"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,13]]},"references-count":45,"alternative-id":["10.1002\/1545-5017.70741"],"URL":"https:\/\/doi.org\/10.1002\/1545-5017.70741","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,13]]},"assertion":[{"value":"2026-06-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70741"}}